We have previously demonstrated that human natural killer (NK) cells are reversibly inhibited by activated monocytes or polymorphonuclear cells through the release of hydrogen peroxide. This provides a mechanism for suppression of natural killing at sites of inflammation. In studies during the first year of this grant we identified a complement fragment, similar to C3c, that served as a soluble mediator for triggering this mechanism of suppression by monocytes. During the second year of this grant we have extensively purified and characterized this fragment and found that it differs slightly from C3c that is produced by other mechanisms (activation of the CR1 receptor plus factor I or action of polymorphonuclear elastase). We have therefore designated this novel fragment C3c', and have shown that it is produced by the action of intact polymorphonuclear cells on opsonized particles. We have examined serum from patients with Sjogren's Syndrome or systemic lupus for factors that suppress NK cell activity, but these have so far been identified only in rare instances. During the next year of support, our specific aims are to: (1) examine the mechanism of action (2) continue our atudies of cloned NK cells and of a rat NK-like tumor with regard to the metabolic effects of C3c', and with particular regard to the effects on arachidonic metabolism. (SR)